This proposal requests support to continue development of a Center of Biomedical Research Excellence in Protein Structure and Function (COBRE-PSF) at the University of Kansas. Our Center was established in October 2002, and includes participants from three additional Kansas Universities. After five years all of our initial goals have been met and, in most cases, surpassed by a wide margin. We have graduated nine junior investigators to independent R01 support, recruited and supported a total of 15 additional junior investigators through replacement and pilot project grants, held six scientific and three grant-writing workshops, and inspired multiple research collaborations. We also remodeled over 6000 sq. feet of space, built a new 17,500 sq. foot Structural Biology Center, inaugurated a new Core dedicated to Bio-NMR, and enacted plans to move COBRE-PSF toward a self-sustaining research center. Our investigators have published over 226 peer-reviewed manuscripts and have received 69 research grants totaling more than $22 million. For the renewal period, our overall Aims for the Center are: 1. To recruit, mentor, and accelerate the career development of outstanding junior scientists 2. To enhance the capabilities of our existing Protein Production Core Laboratory (Core B) 3. To enhance the capabilities of our existing Protein Structure Laboratory (Core C) 4. To build a Bio-NMR Core Laboratory dedicated to Protein NMR studies (Core D) 5. To accelerate the professional and scientific growth of all Center participants through a combination of research meetings, seminars, grant application writing workshops, and scientific workshops. Our long-term goal is to attain a critical mass of successful, independent but collaborative investigators, focused on protein structure and function in health and disease, through which COBRE-PSF will become a self-sustaining enterprise into the future. Lay statement: Great advances in genomics paved the way for identifying the cellular proteins that are ultimately responsible for normal cell functioning and for the dysfunction underlying disease states. Development of therapeutic interventions begins with understanding the proteins involved in diseases, and this requires scientists with outstanding expertise in the study of cellular proteins.